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Biomedical subjects

S Sadoshima

Publications and source records attributed to S Sadoshima.

At least 109 records · Page 6Linked to original sources
PubMed1990

[Effects of alpha- and beta-adrenergic blockers on the lower limits of cerebral blood flow autoregulation in spontaneously hypertensive rats].

The effects of alpha- and beta-adrenergic blockers (phenoxybenzamine, PBZ and propranolol, PPL, respectively) on the cerebral (CBF) and cerebellar (CeBF) blood flow autoregulations were examined in spontaneously hypertensive rats. CBF and CeBF were measured during stepwise hemorrhagic hypotension using hydrogen clearance method. The lower limits of autoregulation for CBF beyond which blood flow was decreased steeply were 72% of the resting blood pressure level in the control, 56% in the PBZ treated group, and 80% in the PPL group. Similar tendency was observed in CeBF. These results indicate that PBZ leads to a downward shift while PPL to a slight upward shift of the lower limits of CBF and CeBF autoregulations, suggesting that alpha-adrenergic blockade has a favorable effect for the maintenance of cerebral blood flow during acute reduction of blood pressure.

Adrenergic alpha-Antagonists↗
PubMed1990

[A case of left internal capsular infarction with auditory hallucination and peculiar amnesia and dysgraphia].

A 46-year-old businessman suddenly became to behave curiously on the morning, September 1, 1988. He forgot how to go through an automatic ticket gate, which he used every day. In his company, he also forgot how to open the cash box, and he wrote a meaningless report for his business. From the night on that day, he had experienced auditory hallucination in which whispering words of some criticism to his performance for a few days. On the next day, he was admitted to a psychiatric hospital because he was suggested to have schizophrenia. By day 6 after the onset, his curious symptoms completely disappeared. However, slight verbal memory disturbance and cognitive dysfunction still remained. Because the brain CT on day 6 showed a small localized subcortical infarction in the left hemisphere he was transferred to our clinic on day 20 to elucidate the relation between the abnormal behavior and the infarction. His blood pressure was 116/64 mmHg and pulse was regular 63/min. He was clear and did not have any neurological deficit. He kept his episodic memory regarding the events at the onset and could almost recall them precisely. Results of standard blood tests, electrocardiogram, ultrasound cardiogram, electroencephalogram as well as cerebral angiography were normal. Computed tomography and magnetic resonance imaging showed an infarcted lesion in the genu of the left caudate nucleus, adjacent to the anterior part of the thalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

Agraphia↗
PubMed1989

Effect of thromboxane synthetase inhibitor on cerebral circulation and metabolism during experimental cerebral ischemia in spontaneously hypertensive rats.

The protective effect of thromboxane synthetase inhibitor, OKY-046, on brain ischemia was studied in spontaneously hypertensive rats. Cerebral ischemia was developed by bilateral carotid artery ligation (BCL) for 1 or 3 h and thereafter, circulation was restored for 15 min. OKY-046, 5 or 30 mg/kg, or saline as control was administered i.v. before BCL. Neither blood pressure nor blood gases were altered by OKY-046 or saline injection. During BCL, cerebral cortical blood flow was reduced to 25 and 15% of the resting value at 30 and 60 min, respectively, and these changes were not different among the groups. In rats with ischemia longer than 1 h, the blood flow was well preserved by OKY-046, 30 mg/kg, to 10-17% of the resting level, thus significantly higher than that (less than 5%) in non-treated rats. After 15 min recirculation, the supratentorial lactate level was lower and adenosine triphosphate (ATP) was higher in OKY-046-treated rats than in the saline-treated ischemic rats. Plasma thromboxane B2 was increased markedly in 1 h ischemic-reperfused rats without treatment and the increase was almost completely inhibited by OKY-046. In contrast, 6-keto-prostaglandin F1 alpha was increased 8.5-fold after ischemia and the increase was not affected by the treatment. OKY-046 seems to have an antiischemic effect on acutely induced cerebral ischemia. Selective inhibition of thromboxane A2 production and an inversely high level of prostaglandin I2 may be an important contribution to protection of the microcirculation during ischemia and preservation of ischemic cerebral metabolism.

Adenosine Triphosphate↗
PubMed1989

Glucose tolerance and insulin secretion in conscious and unrestrained normotensive and spontaneously hypertensive rats.

We compared the glucose tolerance and insulin responses to intravenous (IV) glucose administration of a dose of 1 g/kg body weight in a conscious and unrestrained state of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) with catheters chronically indwelled into artery and vein. Both plasma glucose levels at two minutes and ten minutes following IV glucose load as well as the incremental and total areas of plasma glucose were slightly but significantly lower in SHR than in WKY. Glucose disappearance rate (K value) was 7.7 +/- 0.3%/min in SHR, being slightly but significantly higher than that of 6.8 +/- 0.3%/min in WKY. On the other hand, insulin responses to the glucose load at ten minutes and 30 minutes as well as incremental and total insulin areas were significantly lower in SHR than in WKY. There was no significant difference in insulinogenic index between SHR and WKY. Our observations suggest that in a conscious and unrestrained state, SHR have the greater glucose tolerance associated with reduced insulin secretion than do WKY.

Animals↗
PubMed1989

Cerebrospinal fluid lactate in patients with diabetes mellitus and hypoglycaemic coma.

Cerebrospinal fluid (CSF) lactate and pyruvate concentrations were determined in 20 patients with diabetes mellitus but without disturbance of consciousness and five who recovered from hypoglycaemic coma. CSF lactate was slightly but significantly higher in diabetes mellitus (1.78, SEM 0.04 m mol/l) than that in 15 control subjects (1.40, SEM 0.05 m mol/l). In those who recovered from hypoglycaemic coma, CSF lactate was markedly elevated to 2.45-4.43 m mol/l. CSF glucose concentrations, however, were substantially the same between treated hypoglycaemic and diabetes mellitus groups. These findings indicate that CSF lactate levels increase with glycaemic levels in diabetes mellitus owing to enhanced glucose influx into glycolytic pathway of the brain, and also increases in treated hypoglycaemic coma probably due to mitochondrial dysfunction or damage.

Brain Damage, Chronic↗
PubMed1989

Regional cerebral blood flow and metabolism in patients with transient global amnesia: a positron emission tomography study.

In four patients who experienced transient global amnesia (TGA), clinical features and neuroradiological findings including positron emission tomography (PET) were studied within three months of the episodes, and compared with those in seven cases with cerebral transient ischaemic attacks (TIA). None of TGA patients had a previous history or significant risk factors for the cerebrovascular diseases. Their electroencephalogram, brain CT and angiogram for the head and neck were almost normal. PET study showed better preserved cerebral blood flow and oxygen metabolism in each area of the brain in patients with TGA compared with those with TIA in whom focal reductions of flow and metabolism were evident. These observations suggest that TGA is caused by reversible circulatory and/or metabolic disturbance, of which mechanism might be different from that in TIA.

Amnesia↗
PubMed1989

Cerebral ischemia in spontaneously hypertensive rats with type 2 (noninsulin-dependent) diabetes mellitus, cerebral blood flow and tissue metabolism.

The present study was designed to examine the effect of chronic type 2 (noninsulin-dependent) diabetes mellitus on cerebral blood flow and metabolism during cerebral ischemia induced by bilateral carotid artery occlusion in spontaneously hypertensive rats. Diabetes was produced by streptozotocin treatment in 2-day neonates and the experiment was performed at the age of 5 months. The level of mean arterial pressure was not different between diabetic and nondiabetic rats. At 1 h after ischemia, cerebral blood flow was decreased to 1% of the resting value and supratentorial lactate was increased by 8-fold of control, being virtually the same in both groups of rats. In contrast, reduction of cerebral ATP was much less in diabetic rats (1.64 +/- 0.15 mmol/kg) than in nondiabetic rats (0.74 +/- 0.07 mmol/kg) (p less than 0.001); ATP in nonischemic control is 2.80-2.85 mmol/kg. These results could not be explained by the difference in cerebral blood flow between the groups during ischemia. The results suggest that chronic mild hyperglycemia exerts rather a protective effect on the brain against ischemic insult. Effective utilization of metabolites, such as glucose and ketone bodies, may play an important role to minimize metabolic derangements in the ischemic brain in type 2 diabetic-hyperglycemic rats.

Adenosine Triphosphate↗
PubMed1989

Alpha- and beta-adrenergic receptors of noradrenergic innervation modulate the lower limits of cerebral and cerebellar blood flow autoregulation in spontaneously hypertensive rats.

The effects of alpha- and beta-adrenergic receptors on the lower limits of cerebral (CBF) and cerebellar blood flow (CeBF) autoregulation were examined in spontaneously hypertensive rats. CBF and CeBF were measured during hemorrhagic hypotension in rats treated with adrenergic blockers, phenoxybenzamine (PBZ) or propranolol (PPL), using a hydrogen clearance method. The lower limits for CBF beyond which blood flow was decreased steeply were 72% of resting values in the control, 44 in the PBZ and 80 in the PPL group. Similar tendency was also observed for CeBF. In the control group, the reducing rates of mean arterial pressure (MAP) to decrease CBF by 15 and 30% of the resting values were 33% (58 mm Hg) of the resting MAP and 46% (80 mm Hg), respectively, and those to reduce CeBF to the same extent were 35% (61 mm Hg) and 52% (92 mm Hg), respectively. In the PBZ group, the respective reducing rates of MAP were 52% (71 mm Hg) and 65% (88 mm Hg), respectively, for CBF and 50% (68 mm Hg) and 65% (88 mm Hg), respectively, for CeBF. In contrast, in the PPL group, those rates were 22% (39 mm Hg) and 32% (56 mm Hg), respectively, for CBF, and 23% (40 mm Hg) and 30% (52 mm Hg), respectively, for CeBF, being significantly smaller than those in the control and the PBZ groups (p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Hemorrhagic transformation in cerebral embolism.

We studied the mechanism of hemorrhagic infarction after acute cerebral embolism in 160 patients by brain computed tomography and angiography. Hemorrhagic infarction during the month after the embolic event was evident in 65 patients (40.6%). Initial angiography a median of 1.5 (range 1-60) days after the event revealed occlusion of the cerebral arteries in 117 of 142 patients (82.4%), and reopening of the vessels was observed in 56 (94.9%) of 59 patients who had follow-up angiography a median of 20 (range 3-47) days after the event. The incidence of hemorrhagic infarction was higher in patients greater than or equal to 70 years old (31 of 61, 50.8%) than in those aged 50-69 years (27 of 72, 37.5%) or less than 50 years (seven of 27, 25.9%) (greater than or equal to 70 vs. less than 50, p less than 0.05). In patients with moderate or large infarcts, hemorrhagic infarction developed in 50.0% or 51.5%, respectively, while in those with small infarcts it developed in only 2.9% (p less than 0.05). No correlation was found between hemorrhagic infarction and history of hypertension or blood pressure during the acute stage of stroke. Thrombolytic and/or anticoagulant therapy did not affect the incidence of hemorrhagic infarction (40.0% with vs. 40.7% without therapy) but tended to cause massive hematoma. Our results indicate that hemorrhagic transformation in cerebral embolism is caused not only by reopening of the occluded vessels but also by other factors such as age and size of the infarct. Hypertension per se seems to be less important for hemorrhagic infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Liver, kidney and islet cell tumors in spontaneously hypertensive and normotensive rats treated neonatally with streptozotocin.

We studied the oncogenic action of neonatal streptozotocin (STZ) treatment in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) for 12 months. Two-day-old male neonates were intraperitoneally injected with STZ of which doses were 37.5-75.0 mg/kg for SHR and 100.0-150.0 mg/kg for WKY. The 12-month survival rate was 16 of 22 (73%) in SHR and 10 of 14 (71%) in WKY, respectively. The incidence of tumors in STZ-treated SHR was 27% in liver, 14% in kidney and 5% in liver and kidney, being related to the dose of STZ given, namely, 25% in 37.5 mg/kg, 50% in 50.0 or 62.5 mg/kg and 75% in 75.0 mg/kg. In STZ-treated WKY which survived 12 months, all had tumors, namely, 70% in liver, 20% in kidney and 10% in liver and kidney. Histological features of liver and kidney tumors were characteristic of hepatoma and nephroblastoma, respectively. Islet cell tumor was evident in 4 of 10 (40%) in SHR treated with lower doses of STZ (less than or equal to 50 mg/kg) but not in SHR and WKY treated with higher doses (62.5-150.0 mg/kg). The present study indicates that neonatal STZ treatment has the oncogenic action on liver, kidney and pancreatic islet.

Animals↗
PubMed1989

[A case of systemic lupus erythematosus associated with lateral medullary syndrome and unilateral internuclear ophthalmoplegia].

A rare case of systemic lupus erythematosus (SLE) associated with lateral medullary syndrome and unilateral internuclear ophthalmoplegia was reported. A 15 year old girl was admitted to Kyushu University hospital on 2 September in 1987 because of vertigo, occular symptom, and sensory disturbance. She had noted vertigo since 28 August. On admission she had nystagmus, left Horner syndrome, sensory disturbance of left hemiface and right limbs and trunk and mild hemiparesis of right limbs. She also had a discoid erythema behind the left ear, butterfly rash on her cheek. She developed right internuclear ophthalmoplegia on 6 September. Investigations revealed biological false positive of serological test for syphilis, positive antinuclear antibodies, and prolonged APTT. Peripheral blood cell count and erythrocyte sedimentation rate were normal. There was no proteinuria. Computed tomography and magnetic resonance imaging failed to detect any lesions in the brain. Cerebrospinal fluid cell count was 20/3 and Ig-G index was 17.1%. Her neurological signs were thought to be related to SLE. Lupus anticoagulant might be responsible for the development of impairment of central nervous system (CNS). She was treated with prednisolone, initial dose of 40mg, and the symptoms and signs were improved quickly. Early diagnosis and treatment for SLE with CNS involvement is primarily important.

Adolescent↗
PubMed1989

Morphometrical and biochemical differences of endocrine pancreata between spontaneously hypertensive and normotensive rats with or without neonatal streptozotocin-induced diabetes.

We studied the morphometrical and biochemical changes of endocrine pancreata in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) with or without noninsulin-dependent diabetes mellitus induced by neonatal streptozotocin (STZ) treatment at 4 months of age. Female (2-day-old) neonates were intraperitoneally injected with 62.5 or 75.0 mg/kg of STZ for SHR, 87.5 or 100.0 mg/kg of STZ for WKY, and vehicle for control. In STZ-treated groups, overt hyperglycemia developed in SHR with significantly decreased serum immunoreactive insulin (IRI), whereas in WKY, hyperglycemia was very mild and serum IRI was not lowered. The number and mean size of pancreatic islets did not differ between SHR and WKY, although mean islet size was reduced by half in both compared with that in the corresponding control, respectively. Percentage distribution of insulin-positive B cells in the islet was significantly reduced more in SHR than in WKY (34% of control versus 64% of control, p less than 0.05). Furthermore, pancreatic IRI content was far more reduced in SHR than in WKY (3% of control versus 43% of control, p less than 0.001). In vehicle-treated groups, the glycemic levels and the morphometrical islets did not differ between SHR and WKY. However, serum IRI was significantly lower but pancreatic IRI content was higher in SHR than in WKY. The mechanisms of strain differences between SHR and WKY seen in the present study were discussed.

Animals↗
PubMed1989

[Disturbances of fluid and electrolyte balance in patients with acute stroke].

Serum sodium and potassium concentrations were measured in 196 patients with acute cerebral infarction and 56 with cerebral hemorrhage. All patients were admitted within 7 days of onset and the data within 2 weeks of admission were recorded. The incidences of hypernatremia (serum Na greater than or equal to 149 mEq/l), hyponatremia (less than or equal to 134 mEq/l), hyperkalemia (serum K greater than or equal to 4.8 mEq/l) and hypokalemia (less than or equal to 3.2 mEq/l) were higher in patients with hemorrhage (18, 7, 13 and 14%, respectively) than infarction (4.5, 4.5, 11 and 6%, respectively). The incidences of hypernatremia and hyponatremia in infarction were higher in those who had cortical lesions than in those who had lesions in the basal ganglia or infratentorium. In cerebral hemorrhage, the incidence of hypernatremia was the highest in those with brain stem lesion. Hypernatremia was found in 27% of large sized hematoma, being significantly higher than that of those with medium (16%) or small (1%) hematoma. A similar tendency was also observed in hyponatremia and hyperkalemia. In elderly patients, electrolyte disturbances were more common than in young or middle-aged patients. Renal insufficiency and diabetes mellitus were frequent complications in stroke patients with hypernatremia (42 and 32%, respectively), of which 57% died within one month of admission.

Acute Disease↗
PubMed1988

Mortality and histological findings of the brain during and after cerebral ischemia in male and female spontaneously hypertensive rats.

Mortality and pathological changes of the brain during and after cerebral ischemia induced by bilateral carotid artery occlusion (BCO) were studied in male and female spontaneously hypertensive rats (SHR). Systolic arterial blood pressure at rest was significantly higher in male SHR (228 +/- 13 mm Hg, mean +/- S.E.M.) than female (192 +/- 12) (P less than 0.05). The average survival time during permanent occlusion was 11 +/- 6 h (mean +/- S.D.) in male SHR and 17 +/- 7 in female (P less than 0.005), though the cumulative mortality during 24-h ischemia was not different between male (88%) and female SHR (84%). Severe ischemic changes of nerve cells in the brain, especially in the cortex and hippocampus, were observed in 50% of male SHR at 3-h ischemia, while only 15% was observed in female SHR even after 7-h ischemia. After the temporary ischemia followed by reperfusion for 24 h, the mortality was varied between male and female SHR; 0, 31 and 100% after 1-, 3- and 5-h ischemia, respectively, in male SHR and 0% after 1- to 3-h ischemia and 33% after 5- to 7-h ischemia, respectively, in female. Ischemic changes of the brain tissue, such as acidophilic cytoplasm, nuclear degeneration and intercellular edema, were more frequent and severe in male SHR than female after recirculation following 3- or 5-h ischemia. It is concluded that the mortality and post-ischemic viability seem to be determined by the duration of ischemia and also by the degree of the neuronal damage, and female SHR is more tolerated for ischemic insult in comparison to male SHR.

Animals↗
PubMed1988

Massive striatal dopamine release in acute cerebral ischemia in rats.

Extracellular dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and cerebral blood flow were simultaneously determined using in vivo brain dialysis and a hydrogen clearance method in the striatum of spontaneously hypertensive rats during ischemia and after recirculation. Massive striatal dopamine release was demonstrated in acutely induced ischemic brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Early development of nephropathy in a new model of spontaneously hypertensive rat with non-insulin-dependent diabetes mellitus.

We designed the present study to clarify whether the development of nephropathy was accelerated by a combination of hypertension and non-insulin-dependent diabetes. Spontaneously hypertensive rats with non-insulin-dependent diabetes induced by neonatal streptozotocin treatment (25.0-75.0 mg/kg) were separated into severely or mildly diabetic groups according to their non-fasting plasma glucose levels at 12 weeks of age and the findings were compared with the data on a control group treated with citrate buffer alone. The natural courses of urinary excretion rate of total protein, the molecular composition by sodium dodecyl sulfate polyacrylamide gel electrophoresis with laser densitometer and N-acetyl-beta-D-glucosaminidase were measured in the three groups from 12 weeks until 36 weeks of age. Total urinary protein in the control group decreased with age (p less than 0.05), while in the mildly diabetic group changes were nil; in the severely diabetic group, however, the excretion rates of total urinary protein and high molecular weight protein consistently and progressively increased with age (p less than 0.05). The low molecular weight protein continuously decreased with age in the mildly diabetic and control groups (p less than 0.05), while in the severely diabetic group there was no decrease after 28 weeks of age. The urinary N-acetyl-beta-D-glucosaminidase markedly increased (p less than 0.05) in the severely diabetic group throughout the period compared with findings in the control group, but drastically decreased (p less than 0.05) in the mildly diabetic group with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗